The approval of 3 CDK4/6 inhibitors as treatments for ER+ breast cancer has paved the way for ongoing clinical studies evaluating the utility of these inhibitors in combination with those of other signaling pathways (such as but not limited to BRAF, PI3K and MEK) in multiple tumor types that exhibit reliance on CYCLIN D1/CDK4/RB or other components of the cell cycle such as p16 and p27. This evidence concerns the gene RB1 and breast carcinoma.